In:
American Journal of Hypertension, Oxford University Press (OUP), Vol. 31, No. 2 ( 2018-01-12), p. 205-211
Abstract:
A resequencing study of renal epithelial sodium channel (ENaC) genes was conducted to identify rare variants associated with blood pressure (BP) salt-sensitivity. METHODS The Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low-sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive and 300 most salt-resistant GenSalt participants were selected for the resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were resequenced using capillary-based sequencing methods. Traditional burden tests were utilized to examine association between rare variants and BP salt-sensitivity. Associations of low-frequency and common variants were tested using single-marker analyses. RESULTS Carriers of SCNN1A rare variants had a 0.52 [95% confidence interval (CI): 0.32–0.85] decreased odds of BP salt-sensitivity compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt-sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In single-marker analyses, 3 independent common variants in SCNN1A, rs11614164, rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni correction (P = 4.4 × 10–4, 1.1 × 10–8, and 1.3 × 10–3). Each copy of the minor allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23–1.52) increased odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and rs3741914 was associated with 0.68-fold (95% CI: 0.55–0.84) and 0.69-fold (95% CI: 0.54–0.86) decreased odds of salt-sensitivity, respectively. CONCLUSIONS This study demonstrated for the first time a relationship between rare variants in the ENaC pathway and BP salt-sensitivity. Future replication and functional studies are needed to confirm the findings in this study. CLINICAL TRIAL REGISTRY Trial Number NCT00721721
Type of Medium:
Online Resource
ISSN:
0895-7061
,
1941-7225
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2018
detail.hit.zdb_id:
1479505-X
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